Julia Ojuel

Lack of interaction of apolipoprotein E phenotype with the lipoprotein response to lovastatin or gemfibrozil in patients with primary hypercholesterolemia

The magnitude of serum lipid changes in response to hypolipidemic drugs varies considerably between individuals. These differences may be due to interactions between genetic and environmental factors that effect drug bioavailability or the capacity of the lipid-regulating enzyme and receptor targets to be affected. The apolipoprotein E (apoE) gene locus has been examined in this regard, but reports are conflicting on the effect of its variability on the response to hypolipidemic drugs. We investigated the effect of apoE polymorphism on the serum lipid response to the hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin and the fibric acid derivative gemfibrozil. Lipoprotein changes were assessed after 12 weeks of therapy in 106 patients with primary hypercholesterolemia and combined hyperlipidemia treated with lovastastin and in 63 given gemfibrozil therapy. No significant effect of the apoE phenotypes E3/2, E3/3, or E4/3 on the heterogeneity of lipid responses to either drug was found.

First‐trimester biochemical markers for Down syndrome

The value of maternal serum pregnancy‐associated protein A (PAPP‐A), free and total β human chorionic gonadotrophin (fβhCG, βhCG) and α‐fetoprotein (AFP) in screening for Down syndrome (DS) in early pregnancy has been assessed. To evaluate the different biochemical markers, 32 DS pregnancies and 267 controls were used for AFP, βhCG and PAPP‐A. A subgroup of those (17 DS and 136 controls) were used to evaluate fβhCG. All analytes were determined in fresh serum samples. Our results give support to the feasibility of maternal serum levels of PAPP‐A as the best biochemical marker for DS in the first trimester, and either βhCG or fβhCG as the second marker. No differences were found between βhCG and fβhCG distribution levels as expressed as MoMs in normal and DS pregnancies in this study. Copyright

Combining nuchal translucency with umbilical Doppler velocimetry for detecting fetal trisomies in the first trimester of pregnancy

Objective The aim of our study was to evaluate whether the combined use of umbilical artery pulsatility index (UAPI) and nuchal translucency (NT) measurements would be useful in the prediction of fetal chromosomal abnormalities at 10 to 13 weeks of gestation.

Prevalencia de la depresión posparto en las madres españolas: comparación de la estimación mediante la entrevista clínica estructurada y la escala de depresión posparto de Edimburgo

Fundamento y objetivo: Estimar la prevalencia de la depresion posparto (DPP) en una muestra poblacional mediante dos metodos de evaluacion: la entrevista clinica estructurada para el DSM-IV (SCID) y la medida de autoinforme de la Edinburgh Postnatal Depression Scale (EPDS), asi como identificar el punto de corte del EPDS que proporcione una estimacion sin sesgo de la prevalencia de DPP. Pacientes y metodo: Se incluyo en el estudio a todas las madres (n = 1.191) que, durante el periodo de un ano, acudieron al Servicio de Obstetricia y Ginecologia del Hospital Clinic de Barcelona para realizar la visita de control del puerperio (6 semanas posparto). Se utilizo un metodo en dos fases. En la primera etapa, todas las madres incluidas completaron el EPDS. En la segunda, todas aquellas con una puntuacion en la EPDS de 9 o superior (casos probables de DPP), y una muestra aleatoria del 16% de madres con puntuaciones de la EPDS inferior a 9 fueron evaluadas por una psiquiatra utilizando la entrevista SCID, para establecer el diagnostico de depresion mayor y menor. Se invito a realizar la entrevista SCID a un total de 402 mujeres, de las cuales 68 no quisieron participar. Resultados: La prevalencia de depresion segun la entrevista SCID fue del 10,15% (intervalo de confianza [IC] del 95%, 8,43-11,87). La prevalencia de depresion mayor fue del 3,6% (IC del 95%, 2,55-4,67) y la de depresion menor del 6,5% (IC del 95%, 5,14-7,95). El punto de corte 11/12 de la EPDS permite realizar una estimacion sin sesgo de la tasa de prevalencia de DPP. Conclusiones: El presente estudio justifica la necesidad de utilizar diferentes puntos de corte de la EPDS: el punto de corte 10/11 para identificar la poblacion de riesgo y el 11/12 para estimar la prevalencia en estudios epidemiologicos.

Umbilical artery pulsatility index in early pregnancies with chromosome anomalies

Objective The aim of our study was to obtain measurements of the umbilical artery pulsatility index in pregnancies before invasive procedures for prenatal diagnosis, to investigate its potential prognostic value in predicting chromosomal abnormalities.

FIRST‐TRIMESTER BIOCHEMICAL SCREENING FOR DOWN SYNDROME WITH THE USE OF PAPP‐A, AFP, AND β‐hCG

Biochemical screening for Down syndrome (DS) is well established in the second trimester of pregnancy, but there is little information available on its value in the first trimester. This study describes our preliminary results with biochemical screening for DS in the first trimester of pregnancy in order to evaluate its efficacy at this time. Our study population, including 19 DS pregnancies, was evaluated using maternal serum levels of α‐fetoprotein (AFP), β‐human chorionic gonadotropin (β‐hCG), and pregnancy‐associated plasma protein A (PAPP‐A). At a false positive rate (FPR) of 5 per cent, the detection rate (DR) for DS is 9 per cent for β‐hCG, 18 per cent for AFP, and 66 per cent for PAPP‐A when considering these parameters individually. With different combinations of the analytes, the best detection rates are obtained with the association of PAPP‐A and AFP (85 and 82 per cent DR for a 10 and 5 per cent FPR, respectively). Our data support the value of first‐trimester biochemical screening for DS and that of PAPP‐A as a single marker.

UMBILICAL DOPPLER VELOCIMETRY IN FETUSES WITH TRISOMY 18 AT 10–18 WEEKS' GESTATION

The aim of our study was to obtain measurements of the umbilical artery pulsatility index (PI) in pregnancies before invasive procedures for prenatal diagnosis, in order to investigate its potential prognostic value in predicting trisomy 18. We performed a prospective study including 1785 consecutive women from 10 to 18 weeks with singleton pregnancies undergoing chorionic villus sampling (n=559) or genetic amniocentesis (n=1226) in our unit. Doppler measurements were performed transvaginally (tenth to 13th week of gestation) or transabdominally (14th to 18th week of gestation) immediately before the invasive procedure. In 7 out of 10 fetuses subsequently diagnosed as trisomy 18, the PI was above the 95th centile, providing a detection rate of 70 per cent, a specificity of 95·1 per cent, a positive predictive value of 7·7 per cent, and a negative predictive value of 99·8 per cent. When the 90th percentile was assayed as a cut‐off, the efficacy of PI as a marker of trisomy 18 yielded a sensitivity of 90 per cent and a specificity of 90·4 per cent, with a positive predictive value of 5·2 per cent and a negative predictive value of 99·9 per cent. We suggest that although the use of a single PI measurement for screening purposes needs to be confirmed by further investigation, trisomy 18 fetuses show an abnormal increase in umbilical PI in the first half of pregnancy, and its relation to the early onset of fetal growth retardation needs to be further explored.

Brachycephaly is ineffective for detection of Down syndrome in early midtrimester fetuses

The aim of this study was to assess the value of fetal brachycephaly in the detection of Down syndrome at 13-18 weeks of pregnancy. The cephalic index (CI) was determined in 555 consecutive chromosomally normal fetuses, and in 38 chromosomal abnormalities, prior to amniocentesis. A CI > 0.85 was observed in 14% (2/14) of the fetuses with Down syndrome and in 11% of the normal fetuses. In conclusion, our data show that brachycephaly is not a useful marker for Down syndrome in early midtrimester fetuses.

Limited effectiveness of femur and humerus shortening as markers of Down syndrome in early midtrimester fetuses

This is a prospective screening study addressed to assess the value of femur and humerus shortening in the prenatal detection of Down syndrome. Prior to amniocentesis, 1,543 consecutive pregnancies between 13 and 18 weeks were studied. Femur and humerus shortening were assessed with the use of 6 different ratios, and then correlated with the karyotype obtained in amniotic fluid. Sensitivities achieved for Down syndrome with femur ratios were lower than those using humerus (17-22 vs. 43%) for similar false-positive rates (7-8 vs. 6-8%). The most effective ratio was the observed-to-expected humerus length with 43% sensitivity for a 6% false-positive rate. Combining femur and humerus measurements did not substantially improve the prediction obtained using the best humeral ratio. In conclusion, femur and humerus shortening appears to be of limited value in the detection of Down syndrome.

Doppler assessment of umbilical flow after genetic amniocentesis

The aim of our study was to evaluate the immediate changes on the fetal heart rate (FHR) and the fetal umbilical artery pulsatility index (UPI) after performing genetic amniocentesis. This was a prospective study including 431 consecutive singleton pregnancies between 14 and 18 weeks undergoing genetic amniocentesis in our institution. Doppler measurements were obtained transabdominally before and immediately after the procedure. Structural malformations detected by ultrasound were excluded. Students t-test was performed for comparisons among different groups and observed mean changes. The results showed a significant decrease in FHR post-amniocentesis (mean 1.5 beats, t = 3.47, P < 0.01) and a non-significant elevation in UPI (mean -0.01, t = -0.29, P = 0.77) after the procedure. Differences in FHR could be found when analyzed by each gestational week. These preliminary data suggest that although acute fetal hemodynamic changes are detected after genetic amniocentesis, such changes are unlikely to have clinical relevance. However, it is reasonable to propose the use of Doppler as a method of assessing hemodynamic effects caused by prenatal invasive procedures in order to provide more accurate in vivo research on this issue.